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Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Methods

An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 339 - 351
23 May 2023
Tan J Liu X Zhou M Wang F Ma L Tang H He G Kang X Bian X Tang K

Aims

Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing.

Methods

A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 322 - 332
1 Jun 2020
Zhao H Yeersheng R Kang X Xia Y Kang P Wang W

Aims

The aim of this study was to examine whether tourniquet use can improve perioperative blood loss, early function recovery, and pain after primary total knee arthroplasty (TKA) in the setting of multiple-dose intravenous tranexamic acid.

Methods

This was a prospective, randomized clinical trial including 180 patients undergoing TKA with multiple doses of intravenous tranexamic acid. One group was treated with a tourniquet during the entire procedure, the second group received a tourniquet during cementing, and the third group did not receive a tourniquet. All patients received the same protocol of intravenous tranexamic acid (20 mg/kg) before skin incision, and three and six hours later (10 mg/kg). The primary outcome measure was perioperative blood loss. Secondary outcome measures were creatine kinase (CK), CRP, interleukin-6 (IL-6), visual analogue scale (VAS) pain score, limb swelling ratio, quadriceps strength, straight leg raising, range of motion (ROM), American Knee Society Score (KSS), and adverse events.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 321 - 321
1 Jul 2014
Kang X Wilson D Hodgson A
Full Access

Summary

We found good to excellent reproducibility of in vivo hip joint angle measurements during repeated sitting when derived from registering low-resolution Open MRI imagesets with a reference high-resolution conventional MRI scan, despite only moderate similarity of the segmented volumes.

Keywords: hip, kinematics, MRI, femoroacetabular impingement, repeatability

Introduction

Femoroacetabular impingement (FAI) is a mechanical hip disorder caused by an abnormal bony contact between the femur and acetabulum. Open MRIs can enable studies of FAI under weightbearing, but the resolution of such scans is comparatively low, so it is useful to obtain high resolution (HR) reference scans from a conventional MRI and register lower resolution (LR) open MRI images to the HR images. The purpose of this study was to establish the degree of correspondence between the segmented volumes from the two types of scanner and to estimate the repeatability of joint angle measurements.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_28 | Pages 53 - 53
1 Aug 2013
Ren H Wu K Kang X
Full Access

Despite of the significance of computed tomography (CT) images in surgery planning and guidance, CT scans are not always applicable due to high radiation exposure, particularly risky for children and youth. It is critical to reduce radiation exposure for high sensitive candidates and statistical atlas based approach has therefore been an alternative with minimal radiation exposure.

We addressed the aforementioned challenges through statistical atlas constructions, 3D atlas to 2D radiography registration to get patient-specific models with minimal radiations and multiple-objective optimisation for planning the treatments. Statistical atlas can be employed to construct the global reference map. The atlas then can be registered to a pair of intra-operative fluoroscopy images for constructing a patient-specific model. In this way, we can reduce the radiation exposure to the patients significantly. To characterise shape variations, a statistical shape atlas is constructed using Point Distribution Model, by which a mean shape, modes of shape variation and shape variation are obtained. To construct the patient specific model from the statistical atlas, 3D-2D registration is essential and a back-projected ray based 3D-2D Iterative Closest Point registration method is investigated. Then the treatment planning module for optimal insertion is investigated to avoid critical zone and unnecessary punctures.

The experiment shows the feasibility of the proposed method for atlas-based, image-guided orthopaedic interventions using minimal radiograph and optimal planning. The proposed framework can be extended to other potential applications and one example is for periacetabular osteotomy, particularly for young females which is of great importance to minimise radiation dose during surgical planning and navigation.


This paper presents a methodology for measuring the femoro-pelvic joint angle based on in vivo magnetic resonance imaging (MRI) images taken under weight-bearing conditions. We assess the reproducibility of angle measurements acquired when the subject is asked to repeatedly assume a reference position and perform a voluntary movement.

We scanned a healthy subject in a lying position in a 3T MRI scanner to obtain high resolution (HR) images including two transverse T1-weighted TSE sequence scans at the pelvis and knee and a sagittal T1-weighted dual sense scan at the hip joint. We then scanned the same subject in a weight-bearing configuration in a 0.5T open MRI scanner to obtain related low resolution (LR) images of the femur and acetabulum. Four scan cycles were obtained with the subject being removed and reinserted between cycles in the Open MRI scanner. In each cycle, a block was inserted (up position) and removed (down position) under the subject's foot.

The femur and acetabulum bone models were manually segmented and the models from the LR (sitting) images were registered to the HR (supine) images. The femoroacetabular angles relative to the LR scanning plane for four cycles were calculated. The femoral angle relative to the scanner were quite repeatable (SD < 0.9°), the pelvic angles less so (SD ∼2.6–4.3°). The hip flexion angle ranged from 23°–34° in the down and up positions, respectively, so the block induced a mean angle change in the flexion direction of approximately 11° (SD = 1.7°).

We found that the femoral position could be accurately re-acquired upon repositioning, while the pelvic position was notably more variable. Limb position changes induced by inserting a block under the subject's foot were consistent (standard deviations in the relative attitude angles under 2°). Overall, our measurement method produces plausible measures of both the femoroacetabular angles and the changes induced by the block, and the reproducibility of relative joint changes is good.

ACKNOWLEDGMENTS: Dr. Kang was supported by the National Science and Engineering Research Council of Canada (NSERC) through a Postdoctoral Fellowship and conducted her research at the Centre for Hip Health and Mobility at Vancouver General Hospital, Canada.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLIV | Pages 12 - 12
1 Oct 2012
Kang X Yau W Otake Y Taylor R
Full Access

Anterior Cruciate Ligament (ACL) rupture is one of the commonest injuries in sports medicine. However, the rates of the reported graft re-rupture range from 2–10%, leading to around 3000 to 10000 revision ACL reconstructions in United States per annum. Inaccurate tunnel positions are considered to be one of the commonest reasons leading to failure and subsequent revision surgery. Additionally, there remains no consensus of the optimal position for ACL reconstructions.

The positions of the bone tunnels in patients receiving ACL reconstruction are traditionally assessed using X-rays. It is well known that conventional X-ray is not a precise tool in assessing tunnel positions. Thus, there is a recent trend in using three-dimensional (3D) CT. However, routine CT carries a major disadvantage in terms of significant radiation hazard. In addition, it is both inconvenient and expensive to use CT as a regular assessment tools during the follow-up.

The goal of the present work is to develop a novel 2D-3D registration method using single X-ray image and a surface model. By performing such registration for two post-operative X-rays, we can further calculate the 3D tunnel positions after ACL reconstructions. Our framework consists of five parts: (1) a surface model of the knee, (2) a 2D-3D registration algorithm, (3) a 3D tunnel position calculation, (4) a graphic user interface (GUI), and (5) a semi-transparency rendering. Among them, the crucial part is our 2D-3D registration method that estimates the relative position of the knee model in the imaging coordinate system. Once registered, the 3D position of an ACL tunnel in the knee model is calculated from the imaging geometry. The only interaction required is to mark the ACL tunnels on the X-rays through the GUI.

We propose two 2D-3D registration methods. One is a contour-based method that uses pure geometric information. Most methods in this category accomplish the registration by extracting contours in X-rays, establishing their correspondences on the 3D model, and calculating the registration parameters. Unlike these methods, which need point-to-point correspondences, our method optimises the registration parameters in a statistical inference framework without giving or establishing point-to-point correspondences. Due to the use of the statistical inference, our method is robust to the spurs and broken contours that automatically extracted by the contour detector.

The second method takes into account both the geometric shape of the object and the intensity property (intensity changes) of the image, where the intensity changes can be detected via image gradients. The use of gradient is based on the interpretation that two images are considered similar, if intensity changes occur at the same locations. The angles between the image gradients and the projected surface normals were used as a distance measure. The summation of the measures for all projected model points gives us the gradient term, which we multiply the contour-based measurement. Multiplication is preferred over addition because addition of the terms would require both terms to be normalised.

To evaluate the feasibility of our methods, a simulation study was conducted using Digitally Reconstructed Radiographs (DRR) of a sawbone underwent a single-bundle ACL reconstruction performed by an experienced orthopedic surgeon. The real position of the bone tunnel entry point was obtained using the CT images, which were acquired using a custom-made well-calibrated cone-beam CT. The knee model was built by downsampling and smoothing the high-resolution CT reconstructions. It is important in our experiments to make the model different from the original reconstruction since this simulates the condition in which patient's CT is unavailable. Two DRRs generated from approximately anteroposterior and lateral viewpoints were used. For each DRR, 50 trials of 2D-3D registration were carried out for the femoral part using 50 different initialisations, which were randomly selected from the values independently and uniformly distributed within ±10 degrees and ±10 mm of the ground-truth.

Compared with the ground-truth established using the CT images, our single image contour-based method achieved accurate estimations in rotations and in-plane translations, which were (−0.67±1.38, −0.98±0.84, −0.42±0.71) degrees and (0.11±0.26, −0.06±1.20) mm for the anteroposterior image, and (−0.78±0.76, −0.37±0.87, 0.70±0.88) degrees and (−0.14±0.22, 0.31±0.71) mm for the lateral one, respectively. The same experiments were also performed using the second method. However, it did not produce desirable results in our experiments. The tunnel entry point was then calculated using the averaged registration result of our contour-based method. The entry point of the tunnel was obtained with high accuracy of 1.25 mm distance error from the real position of the entry point.

For the 2D-3D registration, the estimated off-plane translations showed relatively low accuracy. It is well known that the depth can be difficult to be accurately estimated using one single image. As the result showed, the accuracy in rotations and in-plane translations is more important for ACL tunnel position estimation in our framework. As for the image gradient, it is too sensitive to the small perturbation caused by image noises. A more robust way of integrating the gradient information into our contour-based method is required. We propose a novel approach for estimating the 3D position of bone tunnels in ACL reconstruction using two post-operative X-rays. It was tested in a sawbone study using DRRs. The most significant advantage of our approach is to potentially eliminate the necessity of acquiring a patient's CT. The success in developing and validating the proposed workflow will allow convenient and precise assessment of tunnel positions in ACL reconstruction with minimal risk of radiation hazard.